Splenic hamartomas in children.

Splenic hamartomas (SHs) are uncommon, benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images, at surgery, or at autopsy. Since the first case description, in 1861, less than 50 pediatric SH cases have been reported in the literature. In this article, we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with SH. These lesions in children were shown to cause symptoms more often than in the adult population. The observed SH sizes in children ranged from a few millimeters to 18 cm, and the symptomatic lesions were mostly larger or multiple. The most common clinical finding was splenomegaly. Signs of hypersplenism were present in children with a single SH larger than 4.5 cm (diameter range: 4.5-18.0 cm) and in those with multiple hamartomas, ranging from a few millimeters to 5 cm. Eighty percent of patients with available laboratory findings had hematological abnormalities such as anemia, thrombocytopenia, or pancytopenia. Other symptoms and signs included abdominal pain, recurrent infections, fever, night sweats, lethargy, growth retardation, and weight loss. The use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic approach. However, the final diagnosis of SH relies on histopathological evaluation. Surgery, including total or partial splenectomy (PS), is the mainstay of SH management. Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with SH. In the majority of pediatric patients with symptomatic SH, resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.

Targeting B7-H3-A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment.

Recent scientific data recognize the B7-H3 checkpoint molecule as a potential target for immunotherapy of pediatric solid tumors (PSTs). B7-H3 is highly expressed in extracranial PSTs such as neuroblastoma, rhabdomyosarcoma, nephroblastoma, osteosarcoma, and Ewing sarcoma, whereas its expression is absent or very low in normal tissues and organs. The influence of B7-H3 on the biological behavior of malignant solid neoplasms of childhood is expressed through different molecular mechanisms, including stimulation of immune evasion and tumor invasion, and cell-cycle disruption. It has been shown that B7-H3 knockdown decreased tumor cell proliferation and migration, suppressed tumor growth, and enhanced anti-tumor immune response in some pediatric solid cancers. Antibody-drug conjugates targeting B7-H3 exhibited profound anti-tumor effects against preclinical models of pediatric solid malignancies. Moreover, B7-H3-targeting chimeric antigen receptor (CAR)-T cells demonstrated significant in vivo activity against different xenograft models of neuroblastoma, Ewing sarcoma, and osteosarcoma. Finally, clinical studies demonstrated the potent anti-tumor activity of B7-H3-targeting antibody-radioimmunoconjugates in metastatic neuroblastoma. This review summarizes the established data from various PST-related studies, including in vitro, in vivo, and clinical research, and explains all the benefits and potential obstacles of targeting B7-H3 by novel immunotherapeutic agents designed to treat malignant extracranial solid tumors of childhood.

Age-specific causes of upper gastrointestinal bleeding in children.

The etiology of upper gastrointestinal bleeding (UGIB) varies by age, from newborns to adolescents, with some of the causes overlapping between age groups. While particular causes such as vitamin K deficiency and cow's milk protein allergy are limited to specific age groups, occurring only in neonates and infants, others such as erosive esophagitis and gastritis may be identified at all ages. Furthermore, the incidence of UGIB is variable throughout the world and in different hospital settings. In North America and Europe, most UGIBs are non-variceal, associated with erosive esophagitis, gastritis, and gastric and duodenal ulcers. In recent years, the most common causes in some Middle Eastern and Far Eastern countries are becoming similar to those in Western countries. However, variceal bleeding still predominates in certain parts of the world, especially in South Asia. The most severe hemorrhage arises from variceal bleeding, peptic ulceration, and disseminated intravascular coagulation. Hematemesis is a credible indicator of a UGI source of bleeding in the majority of patients. Being familiar with the most likely UGIB causes in specific ages and geographic areas is especially important for adequate orientation in clinical settings, the use of proper diagnostic tests, and rapid initiation of the therapy. The fundamental approach to the management of UGIB includes an immediate assessment of severity, detecting possible causes, and providing hemodynamic stability, followed by early endoscopy. Unusual UGIB causes must always be considered when establishing a diagnosis in the pediatric population because some of them are unique to children. Endoscopic techniques are of significant diagnostic value, and combined with medicaments, may be used for the management of acute bleeding. Finally, surgical treatment is reserved for the most severe bleeding.

B7 homologue 3 as a prognostic biomarker and potential therapeutic target in gastrointestinal tumors.

The most common digestive system (DS) cancers, including tumors of the gastrointestinal tract (GIT) such as colorectal cancer (CRC), gastric cancer (GC) and esophageal cancer (EC) as well as tumors of DS accessory organs such as pancreatic and liver cancer, are responsible for more than one-third of all cancer-related deaths worldwide, despite the progress that has been achieved in anticancer therapy. Due to these limitations in treatment strategies, oncological research has taken outstanding steps towards a better understanding of cancer cell biological complexity and heterogeneity. These studies led to new molecular target-driven therapeutic approaches. Different in vivo and in vitro studies have revealed significant expression of B7 homologue 3 (B7-H3) among the most common cancers of the GIT, including CRC, GC, and EC, whereas B7-H3 expression in normal healthy tissue of these organs was shown to be absent or minimal. This molecule is able to influence the biological behavior of GIT tumors through the various immunological and nonimmunological molecular mechanisms, and some of them are shown to be the result of B7-H3-related induction of signal transduction pathways, such as Janus kinase 2/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase/protein kinase B, extracellular signal-regulated kinase, and nuclear factor-κB. B7-H3 exerts an important role in progression, metastasis and resistance to anticancer therapy in these tumors. In addition, the results of many studies suggest that B7-H3 stimulates immune evasion in GIT tumors by suppressing antitumor immune response. Accordingly, it was observed that experimental depletion or inhibition of B7-H3 in gastrointestinal cancers improved antitumor immune response, impaired tumor progression, invasion, angiogenesis, and metastasis and decreased resistance to anticancer therapy. Finally, the high expression of B7-H3 in most common cancers of the GIT was shown to be associated with poor prognosis. In this review, we summarize the established data from different GIT cancer-related studies and suggest that the B7-H3 molecule could be a promising prognostic biomarker and therapeutic target for anticancer immunotherapy in these tumors.

Abiotrophia defectiva liver abscess in a teenage boy after a supposedly mild blunt abdominal trauma: a case report.

BACKGROUND: A pyogenic liver abscess (PLA) represents a pus-filled cavity within the liver parenchyma caused by the invasion and multiplication of bacteria. The most common offender isolated from the PLA in children is Staphylococcus aureus. Abiotrophia defectiva is a Gram-positive pleomorphic bacterium, commonly found in the oral cavity, intestinal, and genitourinary mucosa as part of the normal microbiota. It has been proven to be an etiological factor in various infections, but rarely in cases of PLA. The case presented here is, to the best of our knowledge, the first pediatric case of PLA caused by A. defectiva. CASE PRESENTATION: A 13-year-old Caucasian boy presented with a two-day history of abdominal pain, fever up to 40 °C, and polyuria. Contrast-enhanced computed tomography (CT) scan revealed a single, multiloculated liver lesion, suggestive of a liver abscess. The boy had sustained a bicycle handlebar injury to his upper abdomen 3 weeks before the symptoms appeared and had been completely asymptomatic until 2 days before admission. He was successfully treated with antibiotic therapy and open surgical drainage. A. defectiva was isolated from the abscess material. Histopathology report described the lesion as a chronic PLA. CONCLUSIONS: A. defectiva is a highly uncommon cause of liver abscess in children. In such cases, various predisposing factors should be considered, including antecedent blunt abdominal trauma.

Possible cytokine biomarkers in pediatric acute appendicitis.

BACKGROUND: Diagnosis of acute appendicitis (AA) and decisions about its treatment remain among the most common dilemmas of pediatric surgical teams. Monitoring of immune response may be of importance for this purpose. Our aim was to measure and analyze serum and peritoneal fluid cytokines, in children who had undergone surgery for suspected AA. METHODS: Prospective investigation of serum and peritoneal fluid cytokine values was performed in 127 consecutive patients. According to the pathohistological findings, patients were divided into three groups: normal/early, uncomplicated and complicated AA. Determination of cytokine concentrations for 20 different cytokines was done using a commercial flow cytometry kit: Human Inflammation 20 plex BMS 819. RESULTS: Statistically significant differences in serum cytokine values between pathohistological groups were found for IP-10, MIP-1α and IL-10. Preoperative cut-off values of IP-10, MIP-1α and IL-10 between groups were obtained using ROC curve analysis. Positive correlations between serum and peritoneal concentrations were recorded for most of the analyzed cytokines. CONCLUSION: IP-10, MIP-1α and IL-10 showed potential in assessment of AA in children. Confirmatory studies with a larger number of patients are required to prove reliability of these biomarkers.

Congenital prepubic urachal-cutaneous fistula.

Congenital prepubic fistula is a very rare congenital anomaly that manifests as a punctiform opening in the midline of the pubic region. According to Campbell, congenital prepubic fistulae are duplicates of the dorsal urethra. Recent investigations have shown that this problem may have a complex etiology. We report a case of a congenital prepubic fistula in 2-month old female neonate, which manifested as a simple punctiform opening in the pubic region, with purulent secretion that resulted from applying pressure to the region. The surgical treatment was successful, and the infant had an uneventful postoperative course of healing.

Ureterocele fenestration with holmium laser in neonates.

AIM: To evaluate the effectiveness of holmium-laser fenestration of intravesical ureteroceles in neonatal period. MATERIAL AND METHOD: We retrospectively analyzed the results of the holmium-laser puncture in ten neonates with intravesical ureterocele, between September 2013 and September 2016. Laser probe was placed through the cystoscope to the lowest and medial portion of the ureterocele, near the bladder floor. Few punctures (4 to 8) were made, until ureterocele has been collapsed. RESULTS: Mean duration of general anesthesia was 16 minutes (range, 10-24) and duration of hospitalization was 1-3 days (mean, 1.3 days). There weren't complications regarding endoscopic treatment. There was the need for retreatment in one (10%) patient. Obstruction was found in one (10%) patient on ultrasound after one month. After three months there was no obstruction on ultrasound in any patient. In patients in whom VCUG was performed, vesicoureteral reflux was not found three months after the surgery. DISCUSSION: The relief of the obstruction, prevention of the vesicoureteral reflux and the urinary tract infection are the reasons for the immediate treatment in the neonatal period. In that way, the preservation of renal function is enabled. The reason for laser fenestration was better endoscopic control of the extensibility of the ablation. The moment of ureterocele collapsing can be visualized directly. CONCLUSIONS: Holmium-laser fenestration is a minimally invasive, highly effective and safe kind of treatment for ureterocele in neonatal period with minimal complication rate. Further clinical studies with a greater number of patients will offer more reliable information regarding this procedure. KEY WORDS: Fenestration, Holmium-laser, Neonates, Ureterocele.

Laser-puncture Versus Electrosurgery-incision of the Ureterocele in Neonatal Patients.

PURPOSE: To compare the holmium-laser puncture and electrosurgery-incision in neonates with intravesical ureterocele. MATERIALS AND METHODS: We retrospectively analyzed the results of laser-puncture of ureterocele (LP group) in 12 patients (mean age 9.8 days, range 4-28) and electrosurgery-incision in 20 patients (ES group) (mean age 10.2 days, range 6-28), treated at our institution. Patients had their records reviewed for preoperative findings, endoscopic procedure description, and postoperative outcomes. RESULTS: There was the need for retreatment in one (8.3%) patient in LP group and in four (20%) patients in ES group (P = .626). Duration of general anesthesia in LP and ES groups was 16 (range, 10-24) minutes and 15 (range, 10-20) minutes, respectively (P = .355). There was no statistically significant difference in terms of hospitalization (LF group one day, ES group 1.35 days) (P = .286). Complications were not found in LP group. There were two (10%) patients with pyelonephritis after the treatment in ES group (P = .516). After one month, obstruction was observed on ultarsound examination in one (8.3%) and two (10%) patients, respectively. After three months, obstructionwas not found in any patient in both groups. After six months, vesicoureteral reflux was found in one (8.3%) patient after laser-puncture of the ureterocele and in 13 (65%) patients after electrosurgery-incision (P = .003). CONCLUSION: Both laser-puncture and electrosurgery-incision endoscopic techniques are highly effective in relieving the obstruction. There is no significant difference regarding hospitalization, need for retreatment and the occurrence of complications. The incidence of de novo vesicoureteral reflux is significantly lower in patients treated with holmium-laser, as well as the need for upper pole partial nephrectomy.

Transverse colon volvulus in neurologicaly imparied patient as an emergency surgical condition: A case report.

Introduction: Transverse colon volvulus is an uncommon cause of bowel obstruction in general. Predisposing factors are mental retardation, dysmotility disorders, chronic constipation and congenital megacolon. Case report: We presented transverse colon volvulus in a 16-year-old boy with cerebral palsy. Chronic constipation in neurologicaly impaired patient was a risk factor predisposing to volvulus. The patient was admitted to the hospital with enormous abdominal distension and acute respiratory insufficiency. A boy was emergently taken to the operating room for exploratory laparotomy. During the surgery, a 360º clockwise volvulus of the transverse colon was found. After reduction of volvulus, an enormous transverse colon was resected and colostomy was formed. In the postoperative period, despite the good functioning of stoma and intraabdominal normotension, numerous and long lasting respiratory problems developed. The patient was discharged from our institution after 8 months. Conclusion: Though very rare in pediatric group, the possibility of a transverse colon volvulus must be considered in the differential diagnosis of acute large bowel obstruction.

Outcome differences between simple and complex gastroschisis.

BACKGROUND: We reviewed differences of the outcome of newborn with simple and complex gastroschisis treated at our institution over the past fifteen years. METHODS: A retrospective cohort study was performed on all infants with gastroschisis treated at the Institute for mother and child health care, Belgrade, between 2001 and 2015 (n=70). Premature infants (<34 weeks of gestation) and babies with birth weight less than 1500 g were excluded (n=5). We compared outcomes in infants with simple gastroschisis and those with complex gastroschisis. An outcome analysis was performed for birth weight, gestational age, gender, mode of defect closure, presence of intestinal necrosis or perforation, reoperation, duration of mechanical ventilation and total parenteral nutrition, presence of bowel pseudoopstraction, sepsis, total duration of hospital stay, mortality rates. RESULTS: Of 65 patients, 15 (23,07%) had complex gastroschisis, including atresia 5 patients (33,3%), ischemic complication 9 patients (60%) and one patient with closing gastroschisis (6,66%). Sixty eight percent underwent primary closure.There was difference between the simple and the complex gastroschisis in duration of mechanical ventilation (P= ,000003), total parenteral nutrition (P= ,000019), bowel pseudoobstruction (P= ,00067), reoperation (P= ,00122), sepsis (P= ,0043), hospital stay (P= ,000198). In the simple gastroschisis group 92% of patients survived to discharge. In the complex gastroschisis group 3 patients died in hospital (P= ,338). CONCLUSIONS: More research should be focused to predict complex gastroschisis and to improve prenatal diagnosis and postnatal management, without a significant increase in morbidity and mortality. KEY WORDS: Complex, Gastroschisis, Outcomes, Simple, Vanishing.

Gastric tube esophageal reconstruction in children with esophageal atresia and caustic stricture Study of clinical value based on 25 single-center. Centre experience.

AIM: The aim of this study was estimation of clinical value of gastric tube esophagoplasty in children based on one single center experience. METHODS: Forty-nine patients with diagnosis of EA (n=22) and caustic esophageal injury (n=27) had undergone reverse gastric tube esophagoplasty during 25 years at our institution. Almost all EA patients received initially gastrostomy and cervical esophagostomy. Majority of CS patients had initially repeated dilatation therapy. Demographics, preoperative features (initial condition, initial treatment and nutritional status) and postoperative features (leakage, stenosis, nutritional status and disease-specific symptoms) were retrospectively reviewed and analyzed. Mean follow up time was 8.2 years. RESULTS: Of 49 patients, 2 patients died and gastric tube failed in one patient. The most common complications were anastomotic leak (52%) and anastomotic stricture (47,8%). Disease-specific symptoms (dysphagia and reflux symptoms) with important clinical manifestations were observed in 10.87% of patients. Preoperatively, all patients were eutrophic. One year after operation 96% of patients stayed eutrophic and two EA patients were malnourished. CONCLUSION: The most common complications such as anastomotic leak and anastomotic stricture may be considered benign. Postoperative nutrition, as good indicator of the procedure's adequacy, for the majority of patients is satisfactory. Gastric tube esophagoplasty is an appropriate alternative for esophageal replacement in children. KEY WORDS: Children, Gastric tube, Esophagoplasty.

Analysis of Prognostic Factors and Mortality in Children with Esophageal Atresia.

OBJECTIVE: The survival rate in newborns with congenital esophageal atresia (EA) is about 85-90 %, and it raises over 95 % in the developed countries. The survival rate in developing countries is much lower and the authors describe their experience with 60 newborns. METHODS: Medical records of 60 newborns (40 boys and 20 girls) with congenital EA were reviewed for the prognostic factors and mortality. RESULTS: The birth weight, mean Apgar score (AS) value, gestational age and birth-operative treatment time had significant influence on the mortality of treated patients (p < 0.05). Thirty five percent newborns had aspirational pneumonia at the moment of hospitalization and 86.7 % of them were operated during the first 48 h. The presence of associated anomalies considerably affected the death rate of treated patients (p < 0.05). The incidence of postoperative complications was similar to those in developed countries but the total mortality was higher (28.3 %); sepsis being the main cause of mortality. The postoperative complications and sepsis significantly influenced the mortality of patients (p < 0.05). CONCLUSIONS: Total mortality in newborns with EA was high; sepsis being the most frequent cause of death. The high total mortality was also caused by prematurity, delay in diagnosis, increased incidence of the aspiration pneumonia and shortage of qualified nurses.